This invention relates to the use of S(+)-flurbiprofen, substantially free of its enantiomorph, R(-)-flurbiprofen, as a topical ophthalmic antiinflammatory agent; and to pharmaceutical compositions comprising S(+)-flurbiprofen substantially free of R(-)-flurbiprofen.
U.S. Pat. No. 4,559,343, issued Dec. 12, 1985, discloses pharmaceutical compositions and methods of treatment employing various known, nonsteroidal analgesic/antiinflammatory agents, including racemic flurbiprofen. To the extent that this patent teaches the ophthalmic pharmacology of racemic flurbiprofen, it is incorporated herein by reference since such disclosure can be applied with efficiency in teaching the pharmaceutical compositions and methods of treatment employing S(+)-flurbiprofen of the present invention. However, as is disclosed in U.S. Pat. No. 4,559,343, flurbiprofen per se at appropriate dosage concentrations for ophthalmic delivery is generally perceived as stinging. Thus, it was the purpose of the disclosure in U.S. Pat. No. 4,559,343 to define formulations which tend to decrease the stinging sensation associated with the application of racemic flurbiprofen to the eye. The pharmaceutical compositions and methods of treatment of U.S. Pat. No. 4,559,343 employ a complex of flurbiprofen and a xanthine derivative, such as, caffeine to achieve the stated objective. The consensus of the clinical experience involving the disclosed xanthine-flurbiprofen compositions of U.S. Pat. No. 4,559,343, however, is that the alleged comfort formulation is only moderately improved. And this is particularly true in situations wherein the exquisitely sensitive cornea is rendered even more sensitive through compromised health or trauma.
With respect to the present invention, it is believed that substantially all of the ophthalmic antiinflammatory activity of racemic flurbiprofen resides in its S(+) enantiomorph. Further, ophthalmic formulations comprising S(+)-flurbiprofen substantially free of R(-)-flurbiprofen and at a concentration level of approximately one-half of the prior recommendations for the racemic mixture are believed to be equivalent in efficacy to prior art formulations containing the racemic mixture at twice that concentration; and it is further believed that such formulations may be employed at this one-half strength level without the acute stinging sensation which attends the use of full strength formulations of racemic flurbiprofen.
The expression, relative to the purity of S(+)-flurbiprofen, that it be "substantially free of R(-)-flurbiprofen" means that the R(-)-flurbiprofen enantiomorph is present in such mixtures at a concentration level of from 0 to 5%. Preparations of such substantially pure forms of S(+)-flurbiprofen can be achieved by known stereo-selective synthesis, or S(+)-flurbiprofen can be isolated from the racemic mixture by known conventional methods, such as, forming diastereoisomeric salts with optically active organic amines.